Fluid secretion in salivary glands is regulated by a sustained elevation of cytoplasmic [Ca2+], which is primarily due to influx. The Ca2+ entry mechanism in salivary gland, and other non-excitable, cells has not yet been determined. This project is directed towards understanding the processes that mediate and regulate Ca2+ influx in salivary gland cells. In this reporting period we have demonstrated that protein (Ser/Thr) phosphorylation is involved in a feedback modulation of Ca2+ influx by Ca2+. Further, we have identified the low affinity Ca2+ influx component as the site of this modulation. We have now demonstrated that isolated basolateral plasma membrane vesicles contain two Ca2+ influx pathways similar to those detected intact parotid acinar cells. Continuing our efforts to purify the proteins involved in these Ca2+ influx pathways, we have used lectin affinity chromatography to partially purify a calcium-permeable cation channel from basolateral plasma membrane vesicles. We have also continued our efforts to understand the damage induced in salivary glands by pathological conditions such as irradiation and chronic inflammation. The physiological status of the damaged cell as well as the possible mechanisms of damage are being investigated. These studies will help CIPCB efforts to devise therapeutic procedures for the recovery of salivary gland function.